Nucleophosmin/B23 is a target of CDK2/cyclin E in centrosome duplication

Cell. 2000 Sep 29;103(1):127-40. doi: 10.1016/s0092-8674(00)00093-3.

Abstract

In animal cells, duplication of centrosomes and DNA is coordinated. Since CDK2/cyclin E triggers initiation of both events, activation of CDK2/cyclin E is thought to link these two events. We identified nucleophosmin (NPM/B23) as a substrate of CDK2/cyclin E in centrosome duplication. NPM/B23 associates specifically with unduplicated centrosomes, and NPM/B23 dissociates from centrosomes by CDK2/cyclin E-mediated phosphorylation. An anti-NPM/B23 antibody, which blocks this phosphorylation, suppresses the initiation of centrosome duplication in vivo. Moreover, expression of a nonphosphorylatable mutant NPM/ B23 in cells effectively blocks centrosome duplication. Thus, NPM/B23 is a target of CDK2/cyclin E in the initiation of centrosome duplication.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Antibodies / pharmacology
  • CDC2-CDC28 Kinases*
  • Centrosome / metabolism*
  • Cyclin E / genetics*
  • Cyclin E / metabolism
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases / genetics*
  • Cyclin-Dependent Kinases / metabolism
  • Gene Deletion
  • Gene Expression Regulation / physiology
  • Mice
  • Microinjections
  • Mutation / genetics
  • Nuclear Proteins / deficiency
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / isolation & purification
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / genetics*
  • Protein-Serine-Threonine Kinases / metabolism

Substances

  • Antibodies
  • Cyclin E
  • Nuclear Proteins
  • nucleophosmin
  • Protein-Serine-Threonine Kinases
  • CDC2-CDC28 Kinases
  • Cdk2 protein, mouse
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases